LAB/IN VITRO RESEARCH e-ISSN 1643-3750 © Med Sci Monit, 2017; 23: 2721-2731 DOI: 10.12659/MSM.905064
Genome-Wide Profiling of miRNA and mRNA Expression in Alzheimer’s Disease
Received: 2017.04.27 Accepted: 2017.05.08 Published: 2017.06.04
Authors’ Contribution: Study Design A Data Collection B Analysis C Statistical Data Interpretation D Manuscript Preparation E Literature Search F Funds Collection G
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Wan-Sheng Chang Yong-Hong Wang Xiao-Tun Zhu Chuan-Jie Wu
1 Department of Neurology, The Second People’s Hospital of Liaocheng, Liaocheng Shandong, P.R. China 2 Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, P.R. China
Wan-Sheng Chang, e-mail:
[email protected], Chuan-Jie Wu, e-mail:
[email protected] This work was supported by a grant from National Natural Science Foundation of China (No. U1404809)
Our study aimed to identify key differentially expressed genes (DEGs) and miRNAs (DEmiRNAs) which can serve as potential biomarkers for diagnosis and therapy of Alzheimer’s disease (AD). We performed miRNA and mRNA integrated analysis (MMIA) to identify DEGs and DEmiRNAs of AD. The ADspecific DEmiRNAs-targets interaction network was contrasted. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed. Q-RT-PCR was used to verify the expression of selected DEGs and DEmiRNAs. We conducted MMIA of AD based on 1 miRNA dataset and 3 mRNA datasets derived from the Gene Expression Omnibus (GEO) database; 1759 DEGs and 12 DEmiRNAs were obtained. DEGs of AD were significantly enriched in Huntington’s disease and AD. LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 were 5 DEGs regulated by 4 DEmiRNAs, including miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. These 4 miRNAs were the top 4 miRNAs covering most DEGs. According to the qRT-PCR results, the expression of PLCb2, NDUFA4, DLG4, miR107, and miR-103a-3p was consistent with our integrated analysis. We concluded that LRP1, CDK5R1, PLCb2, NDUFA4, and DLG4 may play a role in AD regulated by miR-26b-5p, miR-26a-5p, miR-107, and miR-103a-3p. Our findings will contribute to identification of biomarkers and new strategies for drug design for AD treatment. Alzheimer Disease • Biological Markers • Gene Regulatory Networks http://www.medscimonit.com/abstract/index/idArt/905064
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Chang W.-S. et al.: miRNA and mRNA expression in Alzheimer’s disease © Med Sci Monit, 2017; 23: 2721-2731
LAB/IN VITRO RESEARCH
Background
Data analysis
As the most common form of dementia, Alzheimer’s disease (AD) is predicted to affect 11.8% of all people globally by 2050 [1]. Alzheimer’s disease is a fatal neurodegenerative disorder which can be divided into early onset familial AD (EOAD) and late onset Alzheimer’s disease (LOAD) [2]. More than 98% of AD cases are LOAD, which are “sporadic” with no apparent familial recurrence of the disease and typically appears in older individuals (age 65 years and over [3]. It is characterized by progressive neuronal degeneration, pathology of amyloid-b (Ab) deposition (senile plaques, SP), and loss of synapses and formation of neurofibrillary tangles (NFTs) that consist mainly of filaments of hyper-phosphorylated tau [4].
The raw data was preprocessed with background correction. We performed the normalization using the Linear Models for Microarray Data (Limma) package in R. Two-tailed Student’s ttest was used to calculate individual P-values, and the Stouffer test was used to merge individual P-values. Multiple comparison correction was performed by Benjamini & Hochberg method to obtain FDR. We finally identified the DEGs with selected criterion of FDR
